Bone is a composite of biopolymers, principally collagen, and an inorganic component identified as carbonate hydroxyapatite, approximated as (Ca,Mg,Na,M)10(PO4,CO3,HPO4)6(OH,Cl)2.
To date, a wide variety of implant materials have been used to repair, restore, and augment bone. The most commonly used implants include autologous bone, synthetic polymers and inert metals. Protocols using these materials have significant disadvantages that can include patient pain, risk of infection during operations, lack of biocompatibility, cost and the risk that the inserted hardware can further damage the bone. Therefore, a major goal of biomaterial scientists has been to develop novel bone substitutes that can be used as alternatives to these conventional techniques for skeletal repair.
Bone cements, such as cements based on polymethylmethacrylate (PMMA) offer certain advantages in avoiding the use of solid implants, but also have several disadvantages. Methacrylates and methacrylic acid are known irritants to living tissues, and when PMMA-based cements are cured in vivo, free radicals are generated, which can damage surrounding tissues. Moreover, the polymerization reaction for these materials is highly exothermic, and the heat evolved during curing can damage tissues.
The concept and potential advantages of an apatitic or calcium phosphate cement (CPC) as a possible restorative material was first introduced by LeGeros et al in 1982 (“Apatitic Calcium Phosphates: Possible Restorative Materials”, J Dent Res 61(Spec Iss):343).
There are presently several CPC commercial products. CPC have the following advantages: malleability allowing them to adapt to the defect's site and shape. The introduction of injectable calcium phosphate cements greatly improved the handling and delivery of the cements and opened up areas of new applications for the CPC.
CPC systems consist of a powder and a liquid component. The powder component is usually made up of one or more calcium phosphate compounds with or without additional calcium salts. Other additives are included in small amounts to adjust setting times, increase injectability, reduce cohesion or swelling time, and/or introduce macroporosity.
The liquid component may consist of one or more of the following: saline, deionized water, dilute phosphoric acid, dilute organic acids (acetic, citric, succinic acid), sodium phosphate (alkaline or neutral), sodium carbonate or bicarbonate, sodium alginate, sodium bicarbonate, sodium citrate, and/or sodium chondroitin sulphate.
The currently available commercial CPCs suffer from some shortcomings such as absence of macroporosity, slow rate of bioresorbability and a frangible compressive strength. This leads to dangerous stress fractures.
Macroporosity is of great importance for bone regeneration as it facilitates bone cells colonisation of the material, angiogenesis, tissue ingrowth and reabsorption of the material.
Several methods of introducing macroporosity in CPCs have been disclosed.
One of them consists of liberation of CO2 during the reaction of acid and NaHCO3 in providing acid (citric acid) and NaHCO3 or adding acidic sodium phosphate (NaH2PO4) solution to NaHCO3.
Other methods have been recommended as introduction of resorbable fibers, e.g. polygalactin; addition of soluble salts (e.g. calcium chloride and sodium or potassium hydroxide; addition of pore forming agents (e.g., sugar, NaHCO3, calcium salts); using frozen sodium phosphate (NaH2PO4) solution particles.
WO2006030054 suggests foaming of a calcium phosphate cement with the addition of surface active agents and the mechanical beating or stirring of same to form air bubbles providing microporosity.